The antimicrobial peptide cathelicidin protects the urinary tract against invasive bacterial infection

Chromek, Milan; Slamová, Zuzana; Bergman, Peter; Kovács, László; Podracká, Ľudmila; Ehrén, Ingrid; Hökfelt, Tomas; Guðmundsson, Guðmundur H.; Gallo, Richard L.; Agerberth, Birgitta; Brauner, Annelie

doi:10.1038/nm1407

Cited by 563 publications

(566 citation statements)

References 44 publications

Supporting

Mentioning

534

Contrasting

Unclassified

Order By: Relevance

“…Consistent with other data [6][7][8][9] , kidney also expressed different kinds of bactericidal substance ( Supplementary Fig. 6a).…”

Section: Lrrc19 Promotes Expression Of Antimicrobial Substancessupporting

confidence: 91%

See 1 more Smart Citation

LRRC19 expressed in the kidney induces TRAF2/6-mediated signals to prevent infection by uropathogenic bacteria

Song

Cao

et al. 2014

Nat Commun

View full text Add to dashboard Cite

The innate immune-dependent bactericidal effects are critical for preventing microbial colonization in the urinary system. However, the mechanisms involved in establishing innate immune responses in kidney are not completely understood. Here we describe the role of a novel member of the LRR (leucine-rich repeat) class of transmembrane proteins, LRRC19 (LRR-containing 19) in eliminating uropathogenic bacteria. LRRC19 is predominantly expressed in human and mouse kidney tubular epithelial cells and LRRC19-deficient mice are more susceptible to uropathogenic Escherichia coli (UPEC) infection than wild-type or TLR4 knockout mice. Recognition of UPEC by LRRC19 induces the production of cytokines, chemokines and antimicrobial substances through TRAF2-and TRAF6-mediated NF-kB and MAPK signalling pathways. Thus, LRRC19 may be a critical pathogen-recognition receptor in kidney mediating the elimination of UPEC infection.

show abstract

“…Consistent with other data [6][7][8][9] , kidney also expressed different kinds of bactericidal substance ( Supplementary Fig. 6a).…”

Section: Lrrc19 Promotes Expression Of Antimicrobial Substancessupporting

confidence: 91%

“…7), a-defensin-5 (ref. 8) and cathelicidins 9 . In addition, C-type lectins such as Reg3 are also found in the epithelial cells 10 .…”

mentioning

confidence: 99%

LRRC19 expressed in the kidney induces TRAF2/6-mediated signals to prevent infection by uropathogenic bacteria

Song

Cao

et al. 2014

Nat Commun

View full text Add to dashboard Cite

show abstract

“…Recent studies have shown that rather than being a passive barrier, the epithelium is an active participant in the host response to infection through not only the expression and production of proinflammatory cytokines and chemokines that recruit inflammatory cells to the site of infection, but also the expression of antimicrobial peptides and proteins (AMPs) such as b-defensins and LL-37 [30][31][32]. Consistent with previous study using synthetic TLR2 ligand Pam3Cys [18], we showed that saLP stimulated production of IL-6 and IL-8 in a concentration-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

Staphylococcus aureus lipoproteins trigger human corneal epithelial innate response through toll-like receptor-2

Kumar

Gui

et al. 2008

Microbial Pathogenesis

View full text Add to dashboard Cite

Bacterial lipoproteins (LP) are a family of cell wall components found in a wide variety of bacteria. In this study, we characterized the response of HUCL, a telomerase-immortalized human corneal epithelial cell (HCEC) line, to LP isolated from Staphylococcus (S) aureus. S. aureus LP (saLP) prepared by Triton X-114 extraction stimulated the activation of NF-kB, JNK, and P38 signaling pathways in HUCL cells. The extracts failed to stimulate NF-kB activation in HUCL cells after lipoprotein lipase treatment and in cell lines expressing TLR4 or TLR9, but not TLR2, indicating lipoprotein nature of the extracts. saLP induced the up-regulation of a variety of inflammatory cytokines and chemokines (IL-6, IL-8, ICAM-1), antimicrobial molecules (hBD-2, LL-37, and iNOS), and homeostasis genes (Mn-SOD) at both the mRNA level and protein level. Similar inflammatory response to saLP was also observed in primarily cultured HCECs using the production of IL-6 as readout. Moreover, TLR2 neutralizing antibody blocked the saLP-induced secretion of IL-6, IL-8 and hBD2 in HUCL cells. Our findings suggest that saLP activates TLR2 and triggers innate immune response in the cornea to S. aureus infection via production of proinflammatory cytokines and defense molecules. r

show abstract

“…Depletion of neutrophils by using anti-mouse RB6 antibodies was performed as previously described. 33 Briefly, mice received an intravenous injection of 100 g of anti-RB6 antibodies 1 day before bacterial inoculation. Control mice received equivalent amounts of isotype control antibodies in sterile PBS.…”

Section: Depletion or Inactivation Of Neutrophilsmentioning

confidence: 99%

Immunological Mechanisms Underlying the Genetic Predisposition to Severe Staphylococcus aureus Infection in the Mouse Model

Köckritz-Blickwede

Rohde

Oehmcke

et al. 2008

The American Journal of Pathology

122

130

View full text Add to dashboard Cite

Host genetic variations play a significant role in conferring predisposition to infection. In this study, we examined the immune mechanisms underlying the host genetic predisposition to severe Staphylococcus aureus infection in different mouse strains. Whereas C57BL/6 mice were the most resistant in terms of control of bacterial growth and survival, A/J, DBA/2, and BALB/c mice were highly susceptible and succumbed to infection shortly after bacterial inoculation. Other strains (C3H/HeN, CBA, and C57BL/10) exhibited intermediate susceptibility levels. Susceptibility of mice to S. aureus was associated with an inability to limit bacterial growth in the kidneys and development of pathology. Resistance to S. aureus in C57BL/6 mice was dependent on innate immune mechanisms because Rag2-IL2R␥ ؊/؊ C57BL/6 mice, which are deficient in B, T, and NK cells, were also resistant to infection. Indeed, neutrophil depletion or inhibition of neutrophil recruitment rendered C57BL/6 mice completely susceptible to S. aureus, indicating that neutrophils are essential for the observed resistance. Although neutrophil function is not inhibited in A/J mice, expression of neutrophil chemoattractants KC and MIP-2 peaked earlier in the kidneys of C57BL/6 mice than in A/J mice, indicating that a delay in neutrophil recruitment to the site of infection may underlie the increased susceptibility of A/J mice to S.

show abstract

The antimicrobial peptide cathelicidin protects the urinary tract against invasive bacterial infection

Cited by 563 publications

References 44 publications

LRRC19 expressed in the kidney induces TRAF2/6-mediated signals to prevent infection by uropathogenic bacteria

LRRC19 expressed in the kidney induces TRAF2/6-mediated signals to prevent infection by uropathogenic bacteria

Staphylococcus aureus lipoproteins trigger human corneal epithelial innate response through toll-like receptor-2

Immunological Mechanisms Underlying the Genetic Predisposition to Severe Staphylococcus aureus Infection in the Mouse Model

Contact Info

Product

Resources

About